抗抑郁治疗的遗传药理学

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1、抗抑郁治疗的遗传药理学王连生抑郁症的终身患病率为10%~20%，时点患病率为2%~5%，在世界十大常见疾病中该病排行第四。预计在2020年，抑郁障碍在疾病总负担中位居第二。抑郁症流行情况DiagnosticCriteriaforMajordepression(DSM-IV)DepressedmoodFeelingsofhopelessness,worthlessnessandguiltInabilitytothinkorconcentrateDiminishedinterestorpleasureDecreasedorincr

2、easedappetiteWeightlossorweightgainInsomniaorhypersominaFatigueorlossofenergyPsychomotorretardationoragitationRecurrentthoughtofdeathorsuicideFive(ormore)oftheabovesymptomsPersistlongerthan2weeksSignificantimpairmentinsocial,occupationalorotherimportantareaoffunctio

3、ning抑郁症诊断美国精神障碍诊断与统计手册第4版DrugtypeMechanismMAOiIrreversibleinhibitionofMAOAandB.TCANonselectiveinhibitionofNA,5-HTanddopaminereuptakeSSRISelectioninhibitionof5-HTreuptakeSNRISelectioninhibitionofNAand5-HTreuptakeNARISelectioninhibitionofNAreuptakeNaSSAEnhancementof5-

4、HTandNAreleasebyblockageofpresynaptic2adrenergicreceptorSARIBlockageof5-HT2receptorandinhibitionof5-HTreuptakeMAOi,monoamineoxidaseinhibitors;SSRIselective5-HTreuptakeinhibitors;SNRI,5-HTandNAreuptakeinhibitors;NARI:NAuptakeinhibitors;NaSSA,noradrenergicandspecific

5、5-HTantidepressants;SARI,5-HTantagonistandreuptakeinhibitors临床上治疗药物中国精神障碍分类与诊断标准第3版（CCMD-3）推荐一线药物Relapseratewithdrugvs.placeboincontinuationstudies(DunnerDL.2001JClinPsychiatry)DrugWkofTxRelapse,drug(%)Relapse,placebo(%)PvalueFluoxetine522657<0.01Paroxetine521643<0.

6、001Sertraline441346<0.001Cetalopram241131<0.05Mirtazapine20423<0.05Nefazodone361733<0.0001(GeddesJRetal.2003Lancet)治疗失败30-40%部分显效30-40%显著疗效35-45%NemeroffCBetal.2002NatNeurosciTsaiSJetal.2003CurrentpharmacogenomicsStimpsonetal.2003theCochraneDatabaseReviewAbout30-40%

7、ofMDDpatientsdonotrespondsufficientlytoSSRIs(TsaiSJetal.Currentpharmacogenomics2003).Approximately30%ofpeoplesufferingfromclinicallysignificantdepressiveillnessdonotrespondtotheusuallyrecommendeddoseofantidepressants(Stimpsonetal.theCochraneDatabaseReview2003).Antid

8、epressants:currentlimitationsThehistoryofgoodresponsetothatagentbyapersonorafamilymember(SynopsisofPsychiatry.8th).Afamilialtendencytoresp